Lofepramine, sold under the brand names Gamanil, Lomont, and Tymelyt among others, is a tricyclic antidepressant (TCA) which is used to treat depression. The TCAs are so named as they share the common property of having three rings in their chemical structure. Like most TCAs lofepramine is believed to work in relieving depression by increasing concentrations of the neurotransmitters norepinephrine and serotonin in the synapse, by inhibiting their reuptake. It is usually considered a third-generation TCA, as unlike the first- and second-generation TCAs it is relatively safe in overdose and has milder and less frequent side effects. Lofepramine is not available in the United States, Canada, Australia or New Zealand, although it is available in Ireland, Japan, South Africa and the United Kingdom, among other countries. Depression In the United Kingdom, lofepramine is licensed for the treatment of depression which is its primary use in medicine. Lofepramine is an efficacious antidepressant with about 64% patients responding to it. Contraindications To be used with caution, or not at all, for people with the following conditions: Heart disease Impaired kidney or liver function Narrow angle glaucoma In the immediate recovery period after myocardial infarction In arrhythmias (particularly heart block) Mania In severe liver and/or severe renal impairment And in those being treated with amiodarone or terfenadine. Pregnancy and lactation Lofepramine use during pregnancy is advised against unless the benefits clearly outweigh the risks. This is because its safety during pregnancy has not been established and animal studies have shown some potential for harm if used during pregnancy. If used during the third trimester of pregnancy it can cause insufficient breathing to meet oxygen requirements, agitation and withdrawal symptoms in the infant. Likewise its use by breastfeeding women is advised against, except when the benefits clearly outweigh the risks, due to the fact it is excreted in the breast milk and may therefore adversely affect the infant. Although the amount secreted in breast milk is likely too small to be harmful. Side effects The most common adverse effects (occurring in at least 1% of those taking the drug) include agitation, anxiety, confusion, dizziness, irritability, abnormal sensations, like pins and needles, without a physical cause, sleep disturbances (e.g. sleeplessness) and a drop in blood pressure upon standing up. Less frequent side effects include movement disorders (like tremors), precipitation of angle closure glaucoma and the potentially fatal side effects paralytic ileus and neuroleptic malignant syndrome.